The Proteolysis of ECM in Intervertebral Disc Degeneration.

Intervertebral disc (IVD) degeneration (IDD) is a pathological process that commonly occurs throughout the human life span and is a major cause of lower back pain. Better elucidation of the molecular mechanisms involved in disc degeneration could provide a theoretical basis for the development of lumbar disc intervention strategies. In recent years, extracellular matrix (ECM) homeostasis has received much attention due to its relevance to the mechanical properties of IVDs. ECM proteolysis mediated by a variety of proteases is involved in the pathological process of disc degeneration. Here, we discuss in detail the relationship between the IVD as well as the ECM and the role of ECM proteolysis in the degenerative process of the IVD. Targeting ECM proteolysis-associated proteases may be an effective means of intervention in IDD.

An increase in opening of BK(Ca) channels in smooth muscle cells in streptozotocin-induced diabetic mice.

AIM: To investigate the changes of function of large conductance of calcium-activated potassium channels (BK(Ca) channels) in thoracic aortic smooth muscle cells in early stage of streptozotocin (STZ)-induced diabetic C57BL/6J mice. METHODS: Vascular muscle tension in the isolated thoracic aortic rings of mice was compared, and the role of BK(Ca) channels in relaxation of isolated mice thoracic aortic rings induced by acetylcholine (ACh) was determined. Meanwhile, single vascular smooth muscle cells (VSMCs) were isolated by collagenase, and BK(Ca) currents were recorded by patch-clamp single channel recording technique in symmetric high potassium solution. RESULTS: Tetraethylammonium (TEA) 1 mmol/L, a selective calcium-activated potassium channel blocker, caused significant rightward shift in the concentration-response curves of ACh in the isolated thoracic aortic rings of diabetic mice and pD2 value of ACh-induced relaxation was decreased notably after TEA treatment [(6.3+/-0.4) vs (6.9+/-0.5), n=10 rings from 7 mice, P<0.01]. But pD2 value of ACh-induced relaxation in age-matched control mice did not change in presence and absence of TEA 1 mmol/L [(6.4+/-0.15) vs (6.5+/-0.5), n=7 rings from 6 mice, P>0.05]. Furthermore, conductance of BK(Ca) channels in single thoracic aortic smooth muscle cells was decreased [(199+/-15) pS, n=10 cells from 7 mice vs (266+/-11) pS, n=12 cells from 6 mice, P<0.01], but probability of open of BKCa channels was increased [(0.51+/-0.28) vs (0.11+/-0.06), n=6 cells from 6 mice, P<0.01], and the mean closed time in diabetic mice was reduced [(15+/-15) vs (132+/-98), n=6 cells from 6 mice, P<0.05]. CONCLUSION: The opening of BK(Ca) channels was increased in thoracic aortic smooth muscle cells in the early stage of STZ-induced diabetic C57BL/6J mice by reducing mean closed time, but the conductance of BK(Ca) channels was decreased.